EMD-6057
Structure of the E. coli 50S subunit with ErmCL nascent chain
EMD-6057
Single-particle3.9 Å
Deposition: 27/08/2014Map released: 22/10/2014
Last modified: 10/12/2014
Sample Organism:
Escherichia coli K-12
Sample: ErmCL-stalled E. coli ribosome
Fitted models: 3j7z (Avg. Q-score: 0.312)
Deposition Authors: Arenz S, Meydan S, Starosta AL
,
Berninghausen O,
Beckmann R,
Vazquez-Laslop N,
Wilson DN
Sample: ErmCL-stalled E. coli ribosome
Fitted models: 3j7z (Avg. Q-score: 0.312)
Deposition Authors: Arenz S, Meydan S, Starosta AL
,
Berninghausen O,
Beckmann R,
Vazquez-Laslop N,
Wilson DN
Drug-Sensing by the Ribosome Induces Translational Arrest via Active Site Perturbation.
Arenz S,
Meydan S,
Starosta AL ,
Berninghausen O,
Beckmann R,
Vazquez-Laslop N,
Wilson DN
(2014) Mol. Cell , 56 , 446 - 452
,
Berninghausen O,
Beckmann R,
Vazquez-Laslop N,
Wilson DN
(2014) Mol. Cell , 56 , 446 - 452
Abstract:
During protein synthesis, nascent polypeptide chains within the ribosomal tunnel can act in cis to induce ribosome stalling and regulate expression of downstream genes. The Staphylococcus aureus ErmCL leader peptide induces stalling in the presence of clinically important macrolide antibiotics, such as erythromycin, leading to the induction of the downstream macrolide resistance methyltransferase ErmC. Here, we present a cryo-electron microscopy (EM) structure of the erythromycin-dependent ErmCL-stalled ribosome at 3.9 Å resolution. The structure reveals how the ErmCL nascent chain directly senses the presence of the tunnel-bound drug and thereby induces allosteric conformational rearrangements at the peptidyltransferase center (PTC) of the ribosome. ErmCL-induced perturbations of the PTC prevent stable binding and accommodation of the aminoacyl-tRNA at the A-site, leading to inhibition of peptide bond formation and translation arrest.
During protein synthesis, nascent polypeptide chains within the ribosomal tunnel can act in cis to induce ribosome stalling and regulate expression of downstream genes. The Staphylococcus aureus ErmCL leader peptide induces stalling in the presence of clinically important macrolide antibiotics, such as erythromycin, leading to the induction of the downstream macrolide resistance methyltransferase ErmC. Here, we present a cryo-electron microscopy (EM) structure of the erythromycin-dependent ErmCL-stalled ribosome at 3.9 Å resolution. The structure reveals how the ErmCL nascent chain directly senses the presence of the tunnel-bound drug and thereby induces allosteric conformational rearrangements at the peptidyltransferase center (PTC) of the ribosome. ErmCL-induced perturbations of the PTC prevent stable binding and accommodation of the aminoacyl-tRNA at the A-site, leading to inhibition of peptide bond formation and translation arrest.